Complementary Therapies in Medicine (2014) 22, 632—639
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevierhealth.com/journals/ctim
Reduction of surgery rate in endometriosis patients who take Chinese medicine: a population-based retrospective cohort study Shan-Yu Su a,b,∗, Chih-Hsin Muo c,d, Fung-Chang Sung e, Donald E. Morisky f a
Department of Chinese Medicine, China Medical University Hospital, Taichung 40447, Taiwan School of Post-baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan c School of Medicine, China Medical University, Taichung 40402, Taiwan d Management Office for Health Data, China Medical University Hospital, Taichung 40402, Taiwan e Graduate Institute of Clinical Medicine Science and School of Medicine, College of Medicine, China Medical University f Department of Community Health Sciences, UCLA Fielding School of Public Health, Los Angeles, CA 90095-1772, USA Available online 7 July 2014 b
KEYWORDS Endometriosis; Chinese medicine; Surgery
Summary Objectives: Female patients have frequently utilized Chinese medicine (CM) to treat symptoms that could possibly be related to endometriosis. The objective of this population-based retrospective cohort study was to evaluate the relationship between CM use and subsequent surgery among patients with endometriosis. Design: A total of 8,283 CM users were identified among the 22,488 endometriosis patients found in the National Health Insurance reimbursement database between 2000 and 2010. A control group was identified and consisted of 8,283 matched nonusers with the same disease. A Cox proportional regression analysis was performed in order to assess risk factors for surgery for the CM users and nonusers. Results: When compared to nonusers, CM users were significantly less likely to undergo surgery, with a hazard ratio of 0.47 (95% CI = 0.421, 0.534) after adjusting for age, occupation, childbirth
Abbreviations: CI, confidence interval; CM, Chinese medicine; ICD-9-CM, International Classification of Diseases, 9th Revision Clinical Modification; HR, hazard ratio; IR, incidence rate; IRR, incidence rate ratio; LHID, Longitudinal Health Insurance Database; NHI, National Health Insurance. ∗ Corresponding author at: Department of Chinese Medicine, China Medical University Hospital. No. 2 Yuh-Der Road, Taichung 40447, Taiwan. Tel.: +886 4 22052121x1675; fax: +886 4 22365141. E-mail address: [email protected] (S.-Y. Su). http://dx.doi.org/10.1016/j.ctim.2014.06.010 0965-2299/© 2014 Published by Elsevier Ltd.
Reduction of surgery rate in endometriosis patients who take Chinese medicine
633
status, hypermenorrhea, iron-deficient anemia, dysmenorrhea, and amount of conventional medications. Among patients who had undergone surgery, the follow-up time was longer for CM users than for CM nonusers (p < 0.001). Moreover, the most frequently used CM single and formula were Cyperus rotundus and Gui-zhi-fu-ling-wan, respectively. Conclusions: These results suggest that whatever the underlying reason, CM provides an alternative option that reduces the incidence rate of surgery in endometriosis patients. © 2014 Published by Elsevier Ltd.
Background Endometriosis is an estrogen-dependent inflammatory disorder defined by the presence of active endometrial tissue outside the uterine cavity. Asian women are reported to have a higher risk of endometriosis than other races,1 and the prevalence of endometriosis is estimated to be 2.7% in Taiwanese women.2 The most common sites for endometriosis to occur are the ovaries, cul-de-sac, posterior broad ligaments, uterosacral ligaments, the uterus, fallopian tubes, the sigmoid colon and the appendix.3 The implantation of endometrioid mucosa is associated with the main chronic features of the disease, including pelvic pain, severe dysmenorrhea, hypermenorrhea, dyspareunia and infertility, although it may also be asymptomatic.4 The management of endometriosis varies according to the individual, with a multidisciplinary approach, and with goals of pain relief and/or a successful pregnancy for infertile patients.5 For patients with a mild form of the disease, pharmacological therapies are advisable for controlling symptoms so as to avoid side effects and the costs of surgery until menopause,6 when endometriotic implant growth is suppressed as a result of reduced ovarian estrogen production.7 For patients whose symptoms have failed to resolve or have worsened under medical treatment, surgical management is advisable. Conservative surgery, including fulguration, excision, cauterization, and ablation, is recommended for women who have not completed childbearing, since it preserves the uterus and as much ovarian tissue as possible.6 On the other hand, definitive surgery, including hysterectomy, with or without the removal of fallopian tubes and ovaries, is indicated when incapacitating symptoms persist even after conservative therapy, and when pregnancy is not desired.8 However, surgery is always associated with long lasting complications, including fistula formation, adhesion, and sexual dysfunctions, which can last well beyond menopause, sometimes resulting in a negative quality of life outcome.9,10 Chinese medicine (CM) is the most popular complementary alternative medicine in Asian countries and the Taiwanese Government’s National Health Insurance (NHI) covers it.11,12 Based on the NHI database, CM is commonly used by females to treat reproductive system diseases, including menstruation disorders, abnormal bleeding, as well as non-infectious disorders of female genital organs,13—16 which can potentially be caused by endometriosis. However, no population-based evidence has been reported about the benefit of CM in women with endometriosis. Research regarding the effects of CM on subsequent endometriosis-related conventional treatment is also very limited.
This population-based retrospective cohort study followed patients diagnosed with endometriosis from 1996 to 2010, using a national insurance reimbursement database. The association between CM use and the incidence of surgery in women with endometriosis was then evaluated. The results imply the benefits of CM for endometriosis patients from a public health perspective.
Methods Subjects Endometriosis patients were identified according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code 617 from 2000 to 2010 in the Longitudinal Health Insurance Database 2000 (LHID2000). The LHID2000 was set up by Taiwan’s National Health Research Institute and it contains chronological information about one million randomly selected individuals who were beneficiaries from 1996 to 2000.
Study designs The date of the first diagnosis was used as the entry date, and the date of surgery was used as the outcome date. The types of endometriosis-related surgery include hysterectomy, oophorectomy, fulguration, excision, and the electric cauterization of endometriosis. Subjects who had undergone surgery before the entry date were excluded. CM users were defined as subjects who had received an orally administered CM treatment for more than two consecutive weeks. The CM nonuser group consisted of randomly selected patients who had not used CM, and this was matched with the CM user group according to age and to the duration between diagnosis and CM usage at a 1:1 ratio. The endpoint date was defined as the date of surgery, death, withdrawal from the insurance program, or December 31, 2010. The followup time was defined as the period from CM usage to the endpoint date. Examined variables included socio-demographic factors (age, income level, and occupation status), childbirth status, and endometriosis-related co-morbidities, including hypermenorrhea (ICD-9-CM 626.2), iron-deficiency anemia (ICD-9-CM 280), and dysmenorrhea (ICD-9-CM 625.3).
Statistical analysis In terms of categorical and continuous variables, CM users and CM nonusers were compared using chi-square tests and
634
S.-Y. Su et al.
t-tests, respectively, so as to assess any differences. A Cox proportional regression analysis was used to estimate the hazard ratio (HR) and its 95% confidence intervals (CIs) for undergoing surgery. The Kaplan—Meier method was used to plot the cumulative incidence, while the log-rank test was used to test the difference in cumulative rates between CM users and nonusers. The adjusted models were controlled for age, occupation, childbirth status, co-morbidities (hypermenorrhea, iron-deficiency anemia, and dysmenorrhea), and amount of conventional medications. The incidence rate (IR) for surgery (per 1000 person-years) was also calculated. The relationship between the use of CM and uterine surgery was estimated by using the incidence rate ratio (IRR) and the corresponding 95% CI in a Poisson distribution model. All statistical analyses were performed using SAS software, version 9.1 (SAS Institute Inc., Carey, NC), and the significance level was set at a two-tailed p value of less than 0.05.
Results Study subjects A total of 22,488 women diagnosed with endometriosis from 2000 to 2010 were extracted from the LHID2000 database. Among them, 8,283 patients were identified as CM users, and another 8,283 matched patients were identified as CM nonusers. The mean age of CM users and nonusers was 36.3 years. There was no difference in occupation status, co-morbidity of hypermenorrhea, or co-morbidity of irondeficient anemia between CM users and nonusers (Table 1). However, the income level of CM users was higher than that of CM nonusers. In addition, the proportion of patients who had not experienced childbirth, or who were co-morbid with dysmenorrhea was higher among CM users than it was among CM nonusers.
Table 1 Socio-demographic factors and co-morbidities of Chinese medicine (CM) users and nonusers in patients with endometriosis. CM
Age, years 50 Mean ± SD Income, US$ per month 780.8 Mean ± SD Occupation status White collar Blue collar Others Childbirth No Yes Conventional medicine (days/year) 0 1—50 51—100 101—225 >225 Mean ± SD Co-morbidity Hypermenorrhea Iron-deficient anemia Dysmenorrhea
Total N = 16,566
Nonusers N = 8283
Users N = 8283
n
n
%
n
P-value
%
% 0.6945
361 1929 2811 2685 497
2443 1799 2169 1872
4.3 23.3 33.9 32.4 6.0 36.3 ± 9.6
356 1913 2843 2635 536
29.5 21.7 26.2 22.6 651 ± 438
2249 1846 2082 2106
4.3 23.1 34.3 31.8 6.5 36.3 ± 9.6
717 3842 5654 5320 1033
27.2 22.3 25.1 25.4 681 ± 439
4692 3645 3645 3978
4.3 23.2 34.1 32.1 6.2 36.3 ± 9.6 28.3 22.0 25.7 24.0 666 ± 438
5106 2230 947
61.6 26.9 11.4
5228 2177 878
63.1 26.3 10.6
10,334 4407 1825
62.4 26.6 11.0
5893 2390
71.15 28.85
6225 2058
75.15 24.85
12118 4448
73.15 26.85
449 5.42 1057 12.76 1967 23.75 2613 31.55 2197 26.52 2.61 ± 1.16
912 3978 3634 4090 3952
5.51 24.01 21.94 24.69 23.86 2.37 ± 1.23
2045 1110 3700
4059 2210 7071
0.9578
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevierhealth.com/journals/ctim
Reduction of surgery rate in endometriosis patients who take Chinese medicine: a population-based retrospective cohort study Shan-Yu Su a,b,∗, Chih-Hsin Muo c,d, Fung-Chang Sung e, Donald E. Morisky f a
Department of Chinese Medicine, China Medical University Hospital, Taichung 40447, Taiwan School of Post-baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan c School of Medicine, China Medical University, Taichung 40402, Taiwan d Management Office for Health Data, China Medical University Hospital, Taichung 40402, Taiwan e Graduate Institute of Clinical Medicine Science and School of Medicine, College of Medicine, China Medical University f Department of Community Health Sciences, UCLA Fielding School of Public Health, Los Angeles, CA 90095-1772, USA Available online 7 July 2014 b
KEYWORDS Endometriosis; Chinese medicine; Surgery
Summary Objectives: Female patients have frequently utilized Chinese medicine (CM) to treat symptoms that could possibly be related to endometriosis. The objective of this population-based retrospective cohort study was to evaluate the relationship between CM use and subsequent surgery among patients with endometriosis. Design: A total of 8,283 CM users were identified among the 22,488 endometriosis patients found in the National Health Insurance reimbursement database between 2000 and 2010. A control group was identified and consisted of 8,283 matched nonusers with the same disease. A Cox proportional regression analysis was performed in order to assess risk factors for surgery for the CM users and nonusers. Results: When compared to nonusers, CM users were significantly less likely to undergo surgery, with a hazard ratio of 0.47 (95% CI = 0.421, 0.534) after adjusting for age, occupation, childbirth
Abbreviations: CI, confidence interval; CM, Chinese medicine; ICD-9-CM, International Classification of Diseases, 9th Revision Clinical Modification; HR, hazard ratio; IR, incidence rate; IRR, incidence rate ratio; LHID, Longitudinal Health Insurance Database; NHI, National Health Insurance. ∗ Corresponding author at: Department of Chinese Medicine, China Medical University Hospital. No. 2 Yuh-Der Road, Taichung 40447, Taiwan. Tel.: +886 4 22052121x1675; fax: +886 4 22365141. E-mail address: [email protected] (S.-Y. Su). http://dx.doi.org/10.1016/j.ctim.2014.06.010 0965-2299/© 2014 Published by Elsevier Ltd.
Reduction of surgery rate in endometriosis patients who take Chinese medicine
633
status, hypermenorrhea, iron-deficient anemia, dysmenorrhea, and amount of conventional medications. Among patients who had undergone surgery, the follow-up time was longer for CM users than for CM nonusers (p < 0.001). Moreover, the most frequently used CM single and formula were Cyperus rotundus and Gui-zhi-fu-ling-wan, respectively. Conclusions: These results suggest that whatever the underlying reason, CM provides an alternative option that reduces the incidence rate of surgery in endometriosis patients. © 2014 Published by Elsevier Ltd.
Background Endometriosis is an estrogen-dependent inflammatory disorder defined by the presence of active endometrial tissue outside the uterine cavity. Asian women are reported to have a higher risk of endometriosis than other races,1 and the prevalence of endometriosis is estimated to be 2.7% in Taiwanese women.2 The most common sites for endometriosis to occur are the ovaries, cul-de-sac, posterior broad ligaments, uterosacral ligaments, the uterus, fallopian tubes, the sigmoid colon and the appendix.3 The implantation of endometrioid mucosa is associated with the main chronic features of the disease, including pelvic pain, severe dysmenorrhea, hypermenorrhea, dyspareunia and infertility, although it may also be asymptomatic.4 The management of endometriosis varies according to the individual, with a multidisciplinary approach, and with goals of pain relief and/or a successful pregnancy for infertile patients.5 For patients with a mild form of the disease, pharmacological therapies are advisable for controlling symptoms so as to avoid side effects and the costs of surgery until menopause,6 when endometriotic implant growth is suppressed as a result of reduced ovarian estrogen production.7 For patients whose symptoms have failed to resolve or have worsened under medical treatment, surgical management is advisable. Conservative surgery, including fulguration, excision, cauterization, and ablation, is recommended for women who have not completed childbearing, since it preserves the uterus and as much ovarian tissue as possible.6 On the other hand, definitive surgery, including hysterectomy, with or without the removal of fallopian tubes and ovaries, is indicated when incapacitating symptoms persist even after conservative therapy, and when pregnancy is not desired.8 However, surgery is always associated with long lasting complications, including fistula formation, adhesion, and sexual dysfunctions, which can last well beyond menopause, sometimes resulting in a negative quality of life outcome.9,10 Chinese medicine (CM) is the most popular complementary alternative medicine in Asian countries and the Taiwanese Government’s National Health Insurance (NHI) covers it.11,12 Based on the NHI database, CM is commonly used by females to treat reproductive system diseases, including menstruation disorders, abnormal bleeding, as well as non-infectious disorders of female genital organs,13—16 which can potentially be caused by endometriosis. However, no population-based evidence has been reported about the benefit of CM in women with endometriosis. Research regarding the effects of CM on subsequent endometriosis-related conventional treatment is also very limited.
This population-based retrospective cohort study followed patients diagnosed with endometriosis from 1996 to 2010, using a national insurance reimbursement database. The association between CM use and the incidence of surgery in women with endometriosis was then evaluated. The results imply the benefits of CM for endometriosis patients from a public health perspective.
Methods Subjects Endometriosis patients were identified according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code 617 from 2000 to 2010 in the Longitudinal Health Insurance Database 2000 (LHID2000). The LHID2000 was set up by Taiwan’s National Health Research Institute and it contains chronological information about one million randomly selected individuals who were beneficiaries from 1996 to 2000.
Study designs The date of the first diagnosis was used as the entry date, and the date of surgery was used as the outcome date. The types of endometriosis-related surgery include hysterectomy, oophorectomy, fulguration, excision, and the electric cauterization of endometriosis. Subjects who had undergone surgery before the entry date were excluded. CM users were defined as subjects who had received an orally administered CM treatment for more than two consecutive weeks. The CM nonuser group consisted of randomly selected patients who had not used CM, and this was matched with the CM user group according to age and to the duration between diagnosis and CM usage at a 1:1 ratio. The endpoint date was defined as the date of surgery, death, withdrawal from the insurance program, or December 31, 2010. The followup time was defined as the period from CM usage to the endpoint date. Examined variables included socio-demographic factors (age, income level, and occupation status), childbirth status, and endometriosis-related co-morbidities, including hypermenorrhea (ICD-9-CM 626.2), iron-deficiency anemia (ICD-9-CM 280), and dysmenorrhea (ICD-9-CM 625.3).
Statistical analysis In terms of categorical and continuous variables, CM users and CM nonusers were compared using chi-square tests and
634
S.-Y. Su et al.
t-tests, respectively, so as to assess any differences. A Cox proportional regression analysis was used to estimate the hazard ratio (HR) and its 95% confidence intervals (CIs) for undergoing surgery. The Kaplan—Meier method was used to plot the cumulative incidence, while the log-rank test was used to test the difference in cumulative rates between CM users and nonusers. The adjusted models were controlled for age, occupation, childbirth status, co-morbidities (hypermenorrhea, iron-deficiency anemia, and dysmenorrhea), and amount of conventional medications. The incidence rate (IR) for surgery (per 1000 person-years) was also calculated. The relationship between the use of CM and uterine surgery was estimated by using the incidence rate ratio (IRR) and the corresponding 95% CI in a Poisson distribution model. All statistical analyses were performed using SAS software, version 9.1 (SAS Institute Inc., Carey, NC), and the significance level was set at a two-tailed p value of less than 0.05.
Results Study subjects A total of 22,488 women diagnosed with endometriosis from 2000 to 2010 were extracted from the LHID2000 database. Among them, 8,283 patients were identified as CM users, and another 8,283 matched patients were identified as CM nonusers. The mean age of CM users and nonusers was 36.3 years. There was no difference in occupation status, co-morbidity of hypermenorrhea, or co-morbidity of irondeficient anemia between CM users and nonusers (Table 1). However, the income level of CM users was higher than that of CM nonusers. In addition, the proportion of patients who had not experienced childbirth, or who were co-morbid with dysmenorrhea was higher among CM users than it was among CM nonusers.
Table 1 Socio-demographic factors and co-morbidities of Chinese medicine (CM) users and nonusers in patients with endometriosis. CM
Age, years 50 Mean ± SD Income, US$ per month 780.8 Mean ± SD Occupation status White collar Blue collar Others Childbirth No Yes Conventional medicine (days/year) 0 1—50 51—100 101—225 >225 Mean ± SD Co-morbidity Hypermenorrhea Iron-deficient anemia Dysmenorrhea
Total N = 16,566
Nonusers N = 8283
Users N = 8283
n
n
%
n
P-value
%
% 0.6945
361 1929 2811 2685 497
2443 1799 2169 1872
4.3 23.3 33.9 32.4 6.0 36.3 ± 9.6
356 1913 2843 2635 536
29.5 21.7 26.2 22.6 651 ± 438
2249 1846 2082 2106
4.3 23.1 34.3 31.8 6.5 36.3 ± 9.6
717 3842 5654 5320 1033
27.2 22.3 25.1 25.4 681 ± 439
4692 3645 3645 3978
4.3 23.2 34.1 32.1 6.2 36.3 ± 9.6 28.3 22.0 25.7 24.0 666 ± 438
5106 2230 947
61.6 26.9 11.4
5228 2177 878
63.1 26.3 10.6
10,334 4407 1825
62.4 26.6 11.0
5893 2390
71.15 28.85
6225 2058
75.15 24.85
12118 4448
73.15 26.85
449 5.42 1057 12.76 1967 23.75 2613 31.55 2197 26.52 2.61 ± 1.16
912 3978 3634 4090 3952
5.51 24.01 21.94 24.69 23.86 2.37 ± 1.23
2045 1110 3700
4059 2210 7071
0.9578
